In recent years, development of a drug eluting balloon (DEB) in which a balloon catheter is coated with drugs has been actively performed, and it has been reported to be effective in the treatment and prevention of restenosis. The balloon is coated by a coating film including drugs and excipients, and when a blood vessel is dilated, the balloon presses against a blood vessel wall, and it delivers the drugs to target tissue.
In recent years, it has been found that a morphological form of the drugs coated on the balloon surface influences releasing property and tissue transferability of drugs from the balloon surface in a lesion affected area, and it is known that control of the crystal form or amorphous form of drugs is important.
Since it cannot be said that the drug eluting balloon having a coating layer in the related art sufficiently exhibits low toxicity and a high effect on a stenosis inhibition rate when treating a stenosis portion in a blood vessel, a medical device of which the toxicity is even lower and the stenosis inhibiting effect is high is desired.
DEB has an advantage of use because DEB does not leave any foreign bodies in the blood vessels, unlike BMS (bare metal stent) and DES (drug-eluting stent). In particular, although use of stents is not recommended in the treatment of lower limbs, a demand for DEB is required. Meanwhile, a risk for the embolization of downstream peripheral blood vessels is feared which is caused by microparticulates upon use of DEB. Since embolization of peripheral blood vessels could cause a risk of amputation of lower limbs due to necrosis, alleviation of embolization of peripheral blood vessels is clinically significant. The blood vessels in the BTK (below-the-knee) area are positioned to the peripheral, and the diameter of the blood vessels is small. Therefore a risk for the embolization is focused on and DEB is required to have a lower risk of the embolization. It is presumed that this is relevant not only to the number of the microparticulates, but also the size of microparticulates. The larger the size is, the more possibility the microparticulates are distributed in the muscles adjacent downstream peripheral blood vessels. It is thought that this raises the risk of the embolization, and the size of the microparticulates is expected to be small.
To obtain sufficient treatment effects of DEB, it is important to keep the drug concentration to be transferred to the lesion of the vascular tissue and chronological transition of drug concentration. Further, in the initial term to inhibit the proliferation of smooth muscle cells, relatively high drug concentration is necessary in the vascular tissue, although in the final term to non-inhibit endothelial cells growth, prompt clearance of drug from the tissue is required. When these two points are achieved by DEB in terms of a change of drug concentration, DEB can provide superior treatment effects in both efficacy and safety.
One of the features of DEB is to immediately release drug upon the dilation of the balloon in a couple of minutes and to transfer a sufficient amount of the drug to the vascular tissue. If the drug is not transferred uniformly to the entire treated lesion, uniform inhibitory effects cannot be expected to be imparted to the lesion under treatment. Particularly, since the length of lesion in the blood vessels of lower limbs is longer than that of coronary arteries, it is difficult to obtain uniform efficacy in lower limbs.